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1310693-92-5 molecular structure
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N-hydroxy-4-({2-methyl-1H,2H,3H,4H,5H-pyrido[4,3-b]indol-5-yl}methyl)benzamide hydrochloride

ChemBase ID: 73223
Molecular Formular: C20H22ClN3O2
Molecular Mass: 371.86058
Monoisotopic Mass: 371.14005464
SMILES and InChIs

SMILES:
c1c(ccc(c1)Cn1c2c(c3c1cccc3)CN(CC2)C)C(=O)NO.Cl
Canonical SMILES:
ONC(=O)c1ccc(cc1)Cn1c2ccccc2c2c1CCN(C2)C.Cl
InChI:
InChI=1S/C20H21N3O2.ClH/c1-22-11-10-19-17(13-22)16-4-2-3-5-18(16)23(19)12-14-6-8-15(9-7-14)20(24)21-25;/h2-9,25H,10-13H2,1H3,(H,21,24);1H
InChIKey:
LJTSJTWIMOGKRJ-UHFFFAOYSA-N

Cite this record

CBID:73223 http://www.chembase.cn/molecule-73223.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
N-hydroxy-4-({2-methyl-1H,2H,3H,4H,5H-pyrido[4,3-b]indol-5-yl}methyl)benzamide hydrochloride
IUPAC Traditional name
N-hydroxy-4-({2-methyl-1H,3H,4H-pyrido[4,3-b]indol-5-yl}methyl)benzamide hydrochloride
Synonyms
Tubastatin A hydrochloride
CAS Number
1310693-92-5
PubChem SID
162038143
PubChem CID
57336514

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID Price
Selleck Chemicals
S2627 external link Add to cart Please log in.
Data Source Data ID
PubChem 57336514 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 9.802132  H Acceptors
H Donor LogD (pH = 5.5) 0.58047235 
LogD (pH = 7.4) 2.2025433  Log P 2.5402005 
Molar Refractivity 99.337 cm3 Polarizability 38.427925 Å3
Polar Surface Area 57.5 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Storage Condition
-20°C expand Show data source
Target
HDAC expand Show data source
Salt Data
HCL expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals
Selleck Chemicals - S2627 external link
Research Area
Description Cancer
Biological Activity
Description Tubastatin A is a potent HDAC6 inhibitor with IC50 of 15 nM.
Targets HDAC1 HDAC8
IC50 15 nM 854 nM [1]
In Vitro Tubastatin A is substantially selective for all 11 HDAC isoforms and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. In homocysteic acid (HCA) induced neurodegeneration assays, Tubastatin A displays dose-dependent protection against HCA-induced neuronal cell death starting at 5 μM with near complete protection at 10 μM. [1] At 100 ng/mL Tubastatin A increases Foxp3+ T-regulatory cells (Tregs) suppression of T cell proliferation in vitro. [2] Tubastatin A treatment in C2C12 cells would lead to myotube formation impairment when alpha-tubulin is hyperacetylated early in the myogenic process; however, myotube elongation occurs when alpha-tubulin is hyeperacetylated in myotubes. [3] A recent study indicates that Tubastatin A treatment increases cell elasticity as revealed by atomic force microscopy (AFM) tests without exerting drastic changes to the actin microfilament or microtubule networks in mouse ovarian cancer cell lines, MOSE-E and MOSE-L. [4]
In Vivo Daily treatment of Tubastatin A at 0.5mg/kg inhibits HDAC6 to promote Tregs suppressive activity in mouse models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully major histocompatibility complex (MHC)-incompatible cardiac allograft rejection. [2]
Clinical Trials
Features
Protocol
Kinase Assay [1]
Enzyme Inhibition Assays Enzyme inhibition assays are performed by the Reaction Biology Corporation, Malvern, PA, using the Reaction Biology HDAC Spectrum platform. (www.reactionbiology.com) The HDAC1, 2,4, 5, 6, 7, 8, 9, 10, and 11 assays use isolated recombinant human protein; HDAC3/NcoR2 complex is used for the HDAC3 assay. Substrate for HDAC1, 2, 3, 6, 10, and 11 assays is a fluorogenic peptide from p53 residues 379-382 (RHKKAc); substrate for HDAC8 is fluorogenic diacyl peptide based on residues 379-382 of p53 (RHKAcKAc). Acetyl-Lys (trifluoroacetyl)-AMC substrate is used for HDAC4, 5, 7, and 9 assays. Tubastatin A is dissolved in DMSO and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 30 μM. Control Compound Trichostatin A (TSA) is tested in a 10-dose IC50 with 3-fold serial dilution starting at 5 μM. IC50 values are extracted by curve-fitting the dose/response slopes.
Cell Assay [1]
Cell Lines Primary cortical neuron of fetal Sprague-Dawley rats(embryonic day 17)
Concentrations 0-10 μM
Incubation Time 24 hours
Methods Primary cortical neuron cultures are obtained from the cerebral cortex of fetal Sprague-Dawley rats (embryonic day 17) as described previously. All experiments are initiated 24 hours after plating. Under these conditions, the cells are not susceptible to glutamate-mediated excitotoxicity. For cytotoxicity studies, cells are rinsed with warm PBS and then placed in minimum essential medium (Invitrogen) containing 5.5 g/L glucose, 10% fetal calf serum, 2 mM L-glutamine, and 100 μM cystine. Oxidative stress was induced by the addition of the glutamate analogue homocysteate (HCA; 5 mM) to the media. HCA is diluted from 100-fold concentrated solutions that are adjusted to pH 7.5. In combination with HCA, neurons are treated with Tubastatin A at the indicated concentrations. Viability is assessed after 24 hours by MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method.
Animal Study [2]
Animal Models Na?ve CD45RBhi CD4+ CD25- cells (1 × 106) from WT or HDAC6-/- mice Are injected i.p. into B6/Rag1-/-mice.
Formulation Tubastatin A is dissolved in dimethyl sulfoxide (DMSO).
Doses 0.5 mg/kg
Administration Tubastatin A is injected i.p. daily.
References
[1] Butler KV, et al, J Am Chem Soc, 2010, 132(31), 10842-10846.
[2] de Zoeten EF, et al, Mol Cell Biol, 2011, 31(10), 2066-2078.
[3] Di Fulvio S, et al, PloS One, 2011, 6(12):e28563.
[4] Ketene AN, et al, Integr Biol (Camb), 2012, 4(5), 540-549.

PATENTS

PATENTS

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INTERNET

INTERNET

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